BChE is currently used as stoichiometric OP bioscavenger. Due to the approximately 500-fold larger molecular mass of BChE molecules compared to nerve agent OP molecules, very large amounts of highly purified BChE protein are required for effective protection resulting in prohibitively high costs of treatment, thus restricting its application to very small number of exposed individuals.
Currently, the only approved therapies to treat OP poisoning in humans are intramuscular (IM) injections of pyridinium aldoximes, 2PAM, HI6, MMB4 or similar combined with atropine and an anticonvulsant or intravenous injection of a highly purified human butyrylcholinesterase (hBChE).
Pyridinium aldoxime therapy is directed towards nucleophilic reactivation of acetylcholinesterase (AChE) covalently inhibited by OPs to restore catalytic hydrolysis of neurotransmitter acetylcholine (ACh) and aided by protection of muscarinic ACh receptors from excess ACh by atropine. Antidotal reactivation by pyridinium aldoximes has to be initiated by intramuscular (IM) or intravenous (IV) administration, and lasts for relatively short times (e.g., 0.5 to 1 hour). Due to re-inhibition of reactivated AChE by excess lipophilic OPs that remain in the body for longer time than oximes, antidotal therapy, though inexpensive, is not effective in exposure to large OP doses and has to be repeatedly administered.
Intravenous (IV) injection of purified hBChE can covalently conjugate OP molecules that enter the circulation, thus protecting endogenous AChE in target tissues from OP inhibition. Covalent OP-hBChE conjugates are very stable and one catalytic monomer of administered hBChE can effectively destroy only one, about a 500-fold smaller molecule, of OP, thus requiring administration of a large mass of purified hBChE protein for efficient protection. While proven effective, this “stoichiometric bioscavenger” hBChE therapy is prohibitively costly and administration of large amounts of protein by injection is sufficiently impractical for expeditious treatment of large OP exposed populations in field settings.